Hill M E, Creed G A, McMullan T F, Tyers A G, Hilton-Jones D, Robinson D O, Hammans S R
Wessex Neurology Centre, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
Brain. 2001 Mar;124(Pt 3):522-6. doi: 10.1093/brain/124.3.522.
Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder of late onset that commonly presents with ptosis and dysphagia. The genetic basis of the condition has been identified recently as a stable trinucleotide repeat expansion in exon 1 of the poly(A) binding protein 2 gene (PABP2), in which (GCG)(6) is the normal repeat length. The prevalence of OPMD is greatest in patients of French-Canadian origin. It is not clear if expansion repeat length is a reliable test in other populations. In this study, we analysed the phenotypic and genotypic characteristics of 31 patients with OPMD in the UK. Ptosis was the first reported symptom in two-thirds of the patients, and half of the subjects studied had evidence of ophthalmoplegia. All but one family had a pathological expansion in the PABP2 gene, ranging from (GCG)(8) to (GCG)(13). In contrast to the French-Canadian population, (GCG)(10) was almost as common as (GCG)(9), evidence against a strong founder effect in the UK population. There was a weak association between repeat length and age of disease onset. Patients with longer repeat lengths, such as (GCG)(13), developed severe limb weakness early in the disease. We were unable to detect the (GCG)(7) polymorphism in over 200 normal controls, suggesting that the frequency of this expansion is lower than that found in the French-Canadian population. One family was negative for the expansion. Affected members presented with the classical features of OPMD, namely ptosis, dysphagia and cytoplasmic inclusions on muscle biopsy, although with some atypical features, such as early age of onset, high serum levels of creatine kinase and a profound ophthalmoplegia. This family is an example of a GCG expansion-negative oculopharyngeal syndrome requiring further genetic investigation. We conclude that PABP2 analysis is a reliable non-invasive diagnostic test for OPMD in the UK population.
眼咽型肌营养不良症（OPMD）是一种常染色体显性迟发性疾病，通常表现为上睑下垂和吞咽困难。最近已确定该病的遗传基础是聚腺苷酸结合蛋白2基因（PABP2）第1外显子中的稳定三核苷酸重复序列扩增，其中（GCG）（6）为正常重复长度。OPMD在法裔加拿大患者中患病率最高。尚不清楚扩增重复长度在其他人群中是否为可靠的检测指标。在本研究中，我们分析了英国31例OPMD患者的表型和基因型特征。三分之二的患者首次报告的症状为上睑下垂，且半数研究对象有眼肌麻痹的证据。除一个家系外，所有家系的PABP2基因均有病理扩增，范围从（GCG）（8）到（GCG）（13）。与法裔加拿大人群不同，（GCG）（10）几乎与（GCG）（9）一样常见，这表明英国人群中不存在强烈的奠基者效应。重复长度与疾病发病年龄之间存在弱关联。重复长度较长的患者，如（GCG）（13），在疾病早期就出现严重的肢体无力。我们在200多名正常对照中未检测到（GCG）（7）多态性，这表明该扩增的频率低于法裔加拿大人群。有一个家系扩增结果为阴性。患病成员表现出OPMD的典型特征，即上睑下垂、吞咽困难和肌肉活检时的胞质内包涵体，尽管有一些非典型特征，如发病年龄早、血清肌酸激酶水平高和严重的眼肌麻痹。这个家系是一个GCG扩增阴性的眼咽综合征的例子，需要进一步进行基因研究。我们得出结论，PABP2分析是英国人群中OPMD可靠的非侵入性诊断检测方法。
